Behavioral and biological research on drug abuse will be conducted in multidisciplinary inpatient clinical studies of heroin addicts and polydrug users. Goals of the proposed research on narcotics abuse are: (1) to examine the therapeutic efficacy of new compounds which are not antagonists, or opiate-substitutes and do not have addictive potential; (2) to examine the effects of subchronic heroin use (and antagonist use) on neuroendocrine homeostasis; (3) to develop and evaluate a new measure of narcotic addiction liability which can be used safely in both man and animals; (4) to study the time-course of development of tolerance and physical dependence on opiates in man, using a neuroendocrine bioassay system. We also plan to continue studies of narcotic antagonist (naltrexone) treatment for heroin addicts. The proposed research on polydrug use will examine the combined effects of marihuana and other psychoactive drugs on the following: (1) behavioral patterns of polydrug use and the effects of polydrug use on subjective states and objective measures of skilled performance, attention and perception; (2) effects of polydrug use on aggressive behavior and the correlation of observed behaviors with neuroendocrine function; (3) the medical consequences of polydrug abuse as compared and contrasted with the medical consequences of chronic use of a single drug. Findings from the proposed clinical studies should contribute to the improvement of existing drug abuse treatment and prevention strategies, as well as to a better understanding of how drugs affect biological function and behavior in man.